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P113 Predictive value of C1q donor specific antibody in identifying pathologic features of AMR
Journal article   Peer reviewed

P113 Predictive value of C1q donor specific antibody in identifying pathologic features of AMR

Elizabeth H Field, Sarat Kuppachi, Diana Zepada-Orozco and Danniele G Holanda
Human immunology, Vol.77, pp.121-121
09/2016
DOI: 10.1016/j.humimm.2016.07.178

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Abstract

Donor-specific antibody (DSA) correlates with antibody-mediated rejection (AMR), transplant glomerulopathy and graft loss. However, the threshold of when to treat DSA remains a clinical challenge, as it is not clear whether earlier intervention in the AMR process will improve the success of persistently reducing DSA and prolonging outcomes. To address the need for enhanced recognition of AMR diagnosis, we evaluated the predictive value of C1q and conventional IgG DSA levels in identifying AMR features on biopsy. We performed a retrospective quality control study of 39 biopsies from 20 patients with stored serum samples near the time of biopsy. Serum was tested for DSA by C1q using One Lambda SA reagents modified with anti-C1q-biotin plus streptavidin-PE and by conventional IgG. Biopsies were reviewed by a renal pathologist and renal transplant nephrologist who were blinded to immunologic data, and pathologic features of AMR were extracted and classified. Fisher Exact Test was used on categorical data to test significance of correlations between DSA tests and AMR features. Positive and Negative predictive values (PPV, NPV), sensitivity and specificity of IgG DSA and C1q DSA were calculated for different MFI cut-offs. IgG DSA correlated with positive C4d at MFI over 1300 (p<.003) but had poor PPV because of false positive cases of AMR without C4d. C1q DSA correlated with positive C4d on biopsy with cut-off values at or above 150 MFI (p<.023), with cut-off of 700 MFI (p<.001) performing the best (PPV 88.9%, NPV 93.1%, sensitivity 80%, specificity 96.4%). In contrast, IgG DSA correlated with one or more features of AMR at MFI over 1300 (p<.001, PPV 83.3%, NPV 75%, sensitivity 75%, specificity 83.3%), but C1q DSA did not. Using combined MFI values of the four highest DSAs and MFI cutoffs of either IgG >4500 or C1q >600 correlated with and predicted presence of one or more biopsy feature of AMR (p<.001, PPV 90%, NPV 84.2%, sensitivity 85.7%, specificity 88.9%) and identified all cases with C4d staining. Incorporating both IgG and C1q DSA results criteria improved predictability of AMR features on biopsy. These may be useful criteria for establishing earlier pathological or clinical diagnosis of AMR and for developing treatment decision algorithms.

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